The overall objective of this grant proposal is to locate some of the brain synapses whose activation during cognition can be detected at the scalp. Extensive investigations of normal subjects have distinguished (on the basis of scalp topography, task correlates and latency) three major evoked potential components which are not directly related to either sensory stimulation or motor activity: the N2, P3, and slow-wave (SW). During the same task conditions which evoke these "endogenous" scalp potentials, we have found that large potentials are present in the human hippocampus, parahippocampal gyrus, and amygdala. The large amplitude and phase-reversal within the hippocampal formation of these endogenous limbic potentials (ELPs), as well as their correlation with simultaneously recorded unit activity, strongly imply that ELPs are generated by synapses within the hippocampus. In order to locate these synapses more precisely, we propose to determine their laminar distribution, and whether they produce excitation or inhibition of probable hippocampal pyramidal cells. Like the scalp potentials, ELPs are composed of several components, and we propose to distinguish these components and relate them to the scalp components by observing their covariation across task conditions. The possibility that other brain areas also generate endogenous potentials will be tested in direct recordings from inferotemporal, supplementary motor, orbitofrontal, and dorsolateral frontal neocortical sites. Endogenous potentials recorded at the scalp represent potentials passively volume-conducted from specific brain regions. We will test whether these regions include the anterior temporal lobe by recording scalp potentials before and after therapeutic unilateral anterior temporal lobectomy. The ability to noninvasively detect antivity in specific synaptic systems would be useful not only for testing neural models of cognition, but also for probing the neural substrate of normal aging and the various neurological diseases in which endogenous scalp potential latency and amplitude have been found to change